1. Field of the Invention
The present invention relates to the maintenance of catheters in a condition that is substantially free of microbial colonization. Specifically, the invention pertains to the use of a solution having both antimicrobial and anticoagulant properties disposable within the lumen of a catheter.
2. Description of Related Art
Catheters, particularly intravenous (IV) catheters, may be used for infusing fluid, such as a medication, into a patient or withdrawing fluid, such as blood, from a patient. Catheters may include a lumen or reservoir which contains fluid or medication to be injected into, or removed from, a patient's body. In certain configurations an injection port may be provided with the catheter.
Complications associated with catheters include those related to their insertion, such as pneumo/hemothorax, arterial puncture and nerve injury, and those occurring as a consequence of their use, such as thrombosis, infection, and clotting. Catheter occlusions will often occur due to thrombotic complications related to the formation of a fibrin sheath within the lumen of the catheter. Formation of a fibrin sheath may allow for adherence of bacteria to the interior of the catheter lumen and serve as a locus for catheter related infection.
In order to avoid the complication of catheter occlusions between uses, catheters may be filled with a lock solution that includes a concentrated solution of the commonly used anticoagulant heparin. A heparin lock solution fills the entire lumen of a catheter with the solution. The heparin lock solution is injected into the catheter lumen immediately after each use, and is preferably left within the catheter until the catheter is accessed again. The heparin lock solution must be withdrawn from the catheter before the next use so that the heparin lock solution is not introduced into the body of the patient. Typically, heparin lock solutions include up to 10,000 units of heparin per catheter lumen. Infusing this amount of heparin into a patient may result in excessive bleeding.
However, even with the use of a traditional heparin lock solution, the catheter can become occluded between uses from coagulation of blood within the catheter. Blood may be present within the catheter because an inadequate volume of heparin was infused within the catheter lumen, the heparin lock solution diffused from the lumen, or residual blood remains in the lumen. This often results in formation of a thrombus with concomitant loss of flow through the lumen.
Heparin has no substantial antibacterial properties and, in fact, may help to promote growth of bacteria within the biofilm layer of protein on the catheter surfaces. The biofilm proteins on the catheter surfaces can protect bacteria growing within a catheter lumen from antibiotics and white blood cells. Heparin has also been found to induce the loss of platelets and can induce clotting in some patients.
To avoid the complication of catheter occlusions between uses, certain catheters may be filled with lock solutions that include citrate salts such as sodium citrate. While sodium citrate is a known anticoagulant, equivalent to about 20 units/mL of heparin (per internal testing), it does not have antimicrobial activity at low concentration (<10%). This is a problem since administering sodium citrate in high concentrations may result in patient toxicity.
If a catheter implanted within a patient becomes infected, the patient may require additional systemic antibiotic treatment and/or removal of the catheter. The risks of catheter-related infections may vary according to the duration of catheter placement within the body, the site of insertion, anatomic location of blood vessels, improper catheter insertion techniques, and the use of improper types of catheter material.
The majority of serious catheter-related infections are associated with central venous catheters, especially those that are placed in patients in an intensive care unit (ICU). In the ICU setting, the incidence of infection is often higher than in the less acute in-patient or ambulatory setting. Certain catheters, such as pulmonary artery catheters and peripheral arterial catheters, may be accessed multiple times per day for hemodynamic measurements or to obtain samples for laboratory analysis, augmenting the potential for contamination and subsequent clinical infection.
Examples of pathogens most commonly related to catheter related bloodstream infections (CR-BSI) include coagulase-negative organisms, gram-positive pathogens, gram-negative pathogens, and fungal organisms. Specific examples of gram-positive pathogens include Staphylococci organisms, such as Staphylococcus aureus and Staphylococcus epidermidis, species of Enterococci, and species of Bacillus. Gram-negative pathogens include: Pseudomonas aeruginosa, Pseudomonas cepacia E. coli, and species of Klebsiella. Examples of fungal microorganisms commonly related to CR-BSI, include species of Candida, such as Candida albicans. 
In addition, bacterial species are rapidly acquiring resistance to antibiotic therapy including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus, and vancomycin resistant enterococci. 
Once microbial pathogens colonize the interior surface of a catheter lumen, the pathogens may embed in a self-produced extracellular polymeric matrix. Within this matrix, pathogens are protected from host defense and from traditional antibiotics.
Accordingly, a need exists for alternative methods to prevent microbial pathogens from colonizing catheters that additionally provide anticoagulant properties.